The rat is a valuable animal model for the study of transplantation immunology, especially organ (kidney) allograft transplantation. The RT1 histocompatibility system in the rat is considered to be analogous to the major histocompatibility complex (MHC) of man. Studies using recombinant rats have demonstrated two gene regions of the MHC. One region codes for the major serologically defined alloantigen (RT1.A) and the other region codes for genes which control stimulation in mixed-lymphocyte-reaction (MLR), immune-associated (Ia) antigens, and immune response (Ir) genes. However, we and others have reported that certain rat strains (RT-11) identical at the MHC can exhibit immune responses usually associated with major histocompatibility differences such as MLR, rejection of skin allografts and graft vs host reactions. These observations suggested that these immune responses in MHC compatible rat strains may be due to non-RT-1 or minor histocompatibility antigens. An MLR model in which rats histocompatible at the MHC are alloimmunized with each other's lymphoid tissue will be employed to study the biological function of these non-RT-1 or minor histocompatibility antigens. Alloimmunization between RT-1 MHC compatible rats were performed for the following strain pairs: Maxx vs BN, RT-1n; Da vs ACI, RT-1a; Lew vs F344, RT-11. Alloimmunization between the two latter rat strain pairs produced altered reactivity in MLC suggesting differences in non-RT-1 or minor histocompatibility antigens. Experiments with congenic rat strains (Lew . B3 and F344 . B3) will be used to differentiate these two possibilities. Furthermore, the modulatory effects of alloimmunization, e.g., suppression of MLC reactivity may have important biological implication in the modification of the immune response in tissue/organ transplantation.